Phenolic contents, antioxidant and cytotoxic activities of Elaeocarpus floribundus Blume.

Elaeocarpus floribundus is higher plant that has been used as traditional medicine for treating several diseases. There is no previous report on phytochemicals and bioactivity studies of this species. In this investigation, triterpenoids friedelin, epifriedelanol and ß-sitosterol were isolated from its leaves and stem bark. Determination of total phenolic content of methanolic extract of leaves and stem bark was carried out using Folin-Ciocalteu reagent. All extracts and isolated compounds were subjected to screening of antioxidant activity using DPPH free radical scavenging method and cytotoxic activities by MTT assay towards human T4 lymphoblastoid (CEM-SS) and human cervical (HeLa) cancer cells. In the total phenolic content determination, methanolic extract of leaves gave higher value of 503.08±16.71 mg GAE/g DW than stem bark with value of 161.5±24.81 mg GAE/g DW. Polar extracts of leaves and stem bark possessed promising antioxidant activity with methanol extract of stem bark exhibited strongest activity with IC50 value of 7.36±0.01 µg/ml. In the cytotoxic activity assay, only chloroform extract of leaves showed significant activity with IC50 value of 25.6±0.06 µg/ml against CEM-SS cancer cell, while friedelin and epifriedelanol were found to be active against the two cancer cells with IC50 values ranging from 3.54 to 11.45 µg/ml.

Antiproliferative activity of xanthones isolated from Artocarpus obtusus.

An investigation of the chemical constituents in Artocarpus obtusus species led to the isolation of three new xanthones, pyranocycloartobiloxanthone A (1), dihydroartoindonesianin C (2), and pyranocycloartobiloxanthone B (3). The compounds were subjected to antiproliferative assay against human promyelocytic leukemia (HL60), human chronic myeloid leukemia (K562), and human estrogen receptor (ER+) positive breast cancer (MCF7) cell lines. Pyranocycloartobiloxanthone A (1) consistently showed strong cytotoxic activity against the three cell lines compared to the other two with IC(50) values of 0.5, 2.0 and 5.0 µg/mL, respectively. Compound (1) was also observed to exert antiproliferative activity and apoptotic promoter towards HL60 and MCF7 cell lines at respective IC(50) values. The compound (1) was not toxic towards normal cell lines human nontumorigenic breast cell line (MCF10A) and human peripheral blood mononuclear cells (PBMCs) with IC(50) values of more than 30 µg/mL.

Mesua beccariana (Clusiaceae), a source of potential anti-cancer lead compounds in drug discovery.

An investigation on biologically active secondary metabolites from the stem bark of Mesua beccariana was carried out. A new cyclodione, mesuadione, along with several known constituents which are beccamarin, 2,5-dihydroxy-1,3,4-trimethoxy anthraquinone, 4-methoxy-1,3,5-trihydroxyanthraquinone, betulinic acid and stigmasterol were obtained from this ongoing research. Structures of these compounds were elucidated by extensive spectroscopic methods, including 1D and 2D-NMR, GC-MS, IR and UV techniques. Preliminary tests of the in vitro cytotoxic activities of all the isolated metabolites against a panel of human cancer cell lines Raji (lymphoma), SNU-1 (gastric carcinoma), K562 (erythroleukemia cells), LS-174T (colorectal adenocarcinoma), HeLa (cervical cells), SK-MEL-28 (malignant melanoma cells), NCI-H23 (lung adenocarcinoma), IMR-32 (neuroblastoma) and Hep-G2 (hepatocellular liver carcinoma) were carried out using an MTT assay. Mesuadione, beccamarin, betulinic acid and stigmasterol displayed strong inhibition of Raji cell proliferation, while the proliferation rate of SK-MEL-28 and HeLa were strongly inhibited by stigmasterol and beccamarin, indicating these secondary metabolites could be anti-cancer lead compounds in drug discovery.

Anti-tumour promoting activity and antioxidant properties of girinimbine isolated from the stem bark of Murraya koenigii S.

Girinimbine, a carbazole alkaloid isolated from the stem bark of Murraya koenigii was tested for the in vitro anti-tumour promoting and antioxidant activities. Anti-tumour promoting activity was determined by assaying the capability of this compound to inhibit the expression of early antigen of Epstein-Barr virus (EA-EBV) in Raji cells that was induced by the tumour promoter, phorbol 12-myristate 13-acetate. The concentration of this compound that gave an inhibition rate at fifty percent was 6.0 µg/mL and was not cytotoxic to the cells. Immunoblotting analysis of the expression of EA-EBV showed that girinimbine was able to suppress restricted early antigen (EA-R). However, diffused early antigen (EA-D) was partially suppressed when used at 32.0 µg/mL. Girinimbine exhibited a very strong antioxidant activity as compared to a-tocopherol and was able to inhibit superoxide generation in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced differentiated premyelocytic HL-60 cells more than 95%, when treated with the compound at 5.3 and 26.3 µg/mL, respectively. However girinimbine failed to scavenge the stable diphenyl picryl hydrazyl (DPPH)-free radical.

Antioxidant, antimicrobial and tyrosinase inhibitory activities of xanthones isolated from Artocarpus obtusus F.M. Jarrett.

One of the most promising plants in biological screening test results of thirteen Artocarpus species was Artocarpus obtusus FM Jarrett and detailed phytochemical investigation of powdered dried bark of the plant has led to the isolation and identification of three xanthones; pyranocycloartobiloxanthone A (1), dihydroartoindonesianin C (2) and pyranocycloartobiloxanthone B (3). These compounds were screened for antioxidant, antimicrobial and tyrosinase inhibitory activities. Pyranocycloartobiloxanthone A (1) exhibited a strong free radical scavenger towards DPPH free radicals with IC50 value of 2 µg/mL with prominent discoloration observed in comparison with standard ascorbic acid, α-tocopherol and quercetin, The compound also exhibited antibacterial activity against methicillin resistant Staphylococcus aureus (ATCC3359) and Bacillus subtilis (clinically isolated) with inhibition zone of 20 and 12 mm, respectively. However the other two xanthones were found to be inactive. For the tyrosinase inhibitory activity, again compound (1) displayed strong activity comparable with the standard kojic acid.

Phylattrin, a new cytotoxic xanthone from Calophyllum soulattri.

Our continuing studies on secondary metabolites from the stem bark of Calophyllum soulattri has led to the isolation of another new diprenylated xanthone, phylattrin (1), in addition to five other xanthones and two common sterols. The xanthones are soulattrin (2), caloxanthone C (3), macluraxanthone (4), brasixanthone B (5) and trapezifolixanthone (6) while the sterols are stigmasterol (7) and ß-sitosterol (8). The structures of these compounds were determined on the basis of spectroscopic analyses such as 1D and 2D-NMR, HRESIMS, IR and UV. Compounds 1-7 exhibited moderate cytotoxic activities against SNU-1, HeLa, Hep G2, NCI-H23, K562, Raji, LS174T, IMR-32 and SK-MEL-28 cells.

A new furanoxanthone from the stem bark of Calophyllum inophyllum.

The stem bark extracts of Calophyllum inophyllum furnished one new furanoxanthone, inophinnin (1), in addition to inophyllin A (2), macluraxanthone (3), pyranojacareubin (4), 4-hydroxyxanthone, friedelin, stigmasterol, and betulinic acid. The structures of these compounds were determined by spectroscopic analysis of 1D and 2D NMR spectral data ((1)H, (13)C, DEPT, COSY, HMQC, and HMBC) while EI-MS gave the molecular mass. The new xanthone, inophinnin (1), exhibited some anti-inflammatory activity in nitric oxide assay.

A new abietene diterpene and other constituents from Kaempferia angustifolia Rosc.

A new abietene diterpene, kaempfolienol (5S,6S,7S,9S,10S,11R,13S-abiet-8(14)-enepenta-6,7,9,11,13-ol, 1), was isolated from a rhizome extract of Kaempferia angustifolia Rosc. along with the known compounds crotepoxide, boesenboxide, zeylenol, 2'-hydroxy-4,4',6'-trimethoxychalcone, (24S)-24-methyl-5α-lanosta-9(11),25-dien-3ß-ol, ß-sitosterol and ß-sitosterol-3-O-ß-D-glucopyranoside. The structures of all compounds were elucidated on the basis of mass spectroscopic and NMR data. Zeylenol (2), the major constituent of the plant, was derivatized into diacetate, triacetate and epoxide derivatives through standard organic reactions. The cytotoxic activity of compounds 1, 2 and the zeylenol derivatives was evaluated against the HL-60, MCF-7, HT-29 and HeLa cell lines.

Lignans and other constituents from aerial parts of Haplophyllum villosum.

During our phytochemical investigation of Haplophyllum villosum (Rutaceae), a perennial herb from Iran, a new 4,8-diaryl-3,7-dioxobicyclo-(3,3,0)-octane type lignan, eudesmin A (1), together with four known compounds--eudesmin (2), haplamine (3), umbelliferone (4) and scopoletin (5)--were isolated from aerial parts of the plant. The structures of the compounds were elucidated using NMR spectral analysis (¹H-NMR, ¹³C-NMR, HSQC, COSY and HMBC) as well as UV, IR and MS spectra and comparison with previously reported data.

Two new acridone alkaloids from Glycosmis macrantha.

Extraction and chromatographic separation of the extracts of dried stem barks of Glycosmis macrantha lead to isolation of two new acridone alkaloids, macranthanine and 7-hydroxynoracronycine, and a known acridone, atalaphyllidine. The structures of these alkaloids were determined by detailed spectral analysis and also by comparison with reported data.

A novel cyclodione coumarin from the stem bark of Mesua beccariana.

Our ongoing investigations on the stem bark of Mesua beccariana afforded a novel cyclodione coumarin, beccamarin, together with two known xanthones, mesuarianone, mesuasinone, two anthraquinones, 4-methoxy-1,3,5-trihydroxy-anthraquinone and 2,5-dihydroxy-1,3,4-trimethoxyanthraquinone and one coumarin, mammea A/AB. The structures were elucidated by 1D and 2D NMR and MS techniques.

Soulamarin, a new coumarin from stem bark of Calophyllum soulattri.

The extracts of the stem bark of Calophyllum soulattri gave a new pyranocoumarin, soulamarin (1), together with five other xanthones caloxanthone B (2), caloxanthone C (3), macluraxanthone (4), trapezifolixanthone (5) and brasixanthone B (6) one common triterpene, friedelin (7), and the steroidal triterpene stigmasterol (8). The structures of these compounds were established based on spectral evidence (1D and 2D NMR).

Two new xanthones from Calophyllum nodusum (Guttiferae).

The air-dried powdered stem bark of Calophyllum nodusum (Guttiferea) collected from Sandakan (Sabah, Malaysia), was extracted sequentially with hexane, chloroform and methanol. The solvents were removed by rotary evaporator to give dark viscous extracts. Detailed and repeated chromatographic separation of the extracts lead to isolation of two new xanthones, identified as nodusuxanthone and trapezifolixanthone A. Other common terpenoids such as betulinic acid, lupeol, stigmasterol and friedelin were also isolated from the extracts and identified. The structures of the compounds were established by detailed spectral analysis and comparison with previously reported data.

Two new xanthones from Artocarpus obtusus.

Two new xanthones, pyranocycloartobiloxanthone A (1) and dihydroartoindonesianin C (2), were isolated from the stem bark of Artocarpus obtusus Jarrett by chromatographic separation. Their structures were determined by using spectroscopic methods and comparison with known related compounds. Pyranocycloartobiloxanthone A (1) showed strong free radical scavenging activity by using DPPH assay as well as cytotoxicity towards K562, HL-60, and MCF7 cell lines.

Pellitorine, a potential anti-cancer lead compound against HL6 and MCT-7 cell lines and microbial transformation of piperine from Piper Nigrum.

Pellitorine (1), which was isolated from the roots of Piper nigrum, showed strong cytotoxic activities against HL60 and MCT-7 cell lines. Microbial transformation of piperine (2) gave a new compound 5-[3,4-(methylenedioxy)phenyl]-pent-2-ene piperidine (3). Two other alkaloids were also found from Piper nigrum. They are (E)-1-[3',4'-(methylenedioxy)cinnamoyl]piperidine (4) and 2,4-tetradecadienoic acid isobutyl amide (5). These compounds were isolated using chromatographic methods and their structures were elucidated using MS, IR and NMR techniques.

Furoquinoline alkaloids from Melicope bonwickii (F.Muell.) T.Hartley.

Investigation on the leaves of Melicope bonwickii (F.Muell.) T.Hartley (Rutaceae) afforded a new 7-(2'-hydroxy-3'-chloroprenyloxy)-4-methoxyfuroquinoline (1) together with the known 7-(2',3'-epoxyprenyloxy)-4-methoxyfuroquinoline (2), evellerine (3) kokusaginine (4) and an amide aurantiamide acetate (5). Compounds 1 and 2 showed significant activity against cervical cell lines (Hela).

A new coumarin and triterpenes from Malaysian Micromelum minutum.

A new coumarin, 8,4''-dihydroxy-3'',4''-dihydrocapnolactone-2',3'-diol (1) and two known triterpenes, 5(6)-gluten-3-one (2) and 5(6)-gluten-3alpha-ol (3) were isolated from the leaves of Micromelum minutum (Rutaceae) collected from Sepilok, Sabah, Malaysia and their structures were characterized by spectroscopic methods.

A New Bioactive Secondary Metabolite from Artocarpus elasticus.

Detailed phytochemical investigation has been carried out on the bark of Artocarpus elasticus Reinw. ex Blume, which led to the isolation of artonin E (1), a new dihydrobenzoxanthone derivative named elastixanthone (2), cycloartobiloxanthone (3) and artobiloxanthone (4). Structures of these compounds were elucidated on the basis of various spectroscopic (UV, IR, ID-NMR and 2D-NMR) and MS data. Compounds 1-3 displayed outstanding scavenging activity for 1,1-diphenylpicrylhydrazyl (DPPH) with IC5o values of 11.5, 21.6 and 40.0 µg/mL, respectively. In addition, compounds 1-3 displayed broad spectrum antimicrobial activities against thirteen different bacterial strains when tested using the disc diffusion assay. Cytotoxic screening revealed that artonin E (1). constantly exhibited strong cytotoxic activity against human estrogen receptor (ER+) positive breast cancer (MCF-7) and human estrogen receptor (ER-) negative (MDA-MB 231) cells in comparison with the other two, with IC50 values of 2.6 and 13.5 µg/mL, respectively, without being toxic towards the WRL68 (human normal liver) cell line (IC50 value more than 30 [µg/mL). However, the compound was inactive against HepG2 (human liver carcinoma) cancer cells.

Coumarins from Malaysian Micromelum minutum.

In a continuation of our study of the Rutaceae, detailed chemical investigation on Micromelum minutum (Rutaceae) collected from Sepilok, Sabah, Malaysia gave four new coumarins. The structures of the coumarins have been fully characterised by spectroscopic methods as 3",4"-dihydrocapnolactone 1, 2',3'-epoxyisocapnolactone 2, 8-hydroxyisocapnolactone-2',3'-diol 3 and 8-hydroxy-3",4"-dihydrocapnolactone-2',3'-diol 4.

A new flavonoid and sulphur-containing amides from Glycosmis chlorosperma.

A new flavonoid, dihydroglychalcone-A, was isolated from the leaves extract of Glycosmis chlorosperma in addition to two known sulphur-containing amides, dambullin and gerambullin. The structure of the new compound was assigned as 2'-hydroxy-4,6'-dimethoxy-3',4'-(2",2"-dimethylpyrano)dihydrochalcone. The extract of the leaves was also found to exhibit antimicrobial and cytotoxic activities.